Professor of Molecular Biology and Biochemistry

Chair, Molecular Biology and Biochemistry

sholmes@wesleyan.edu

Our research focuses on a fundamental question: how does the structure of a eukaryotic chromosome influence gene expression?  The primary structural component of the eukaryotic chromosome is the nucleosome, composed of four different histone proteins.  Each of these histones can be modified to create nucleosomes with unique characteristics, including the ability to activate or repress gene expression.  Therefore, a histone code determines accessibility to the genetic code found in the DNA. Our experiments on gene regulation take advantage of the advanced molecular genetics of budding yeast, a single-celled eukaryote.   A powerful combination of classical genetics, molecular biology, and biochemistry can be applied to address the biology of yeast, and these findings are generally applicable to all eukaryotes.  Yeast uses a mechanism known as silencing to regulate expression of genes that dictate the developmental program of the cell. Silencing is achieved by formation of the yeast equivalent of heterochromatin, a repressive chromatin structure.  Once established, this gene repression is epigenetically inherited; the expression state becomes a permanent, heritable property of the gene.

Cell cycle-dependent establishment of transcriptional silencing
We are using an inducible system to study the establishment of silencing in yeast.  We have found that the onset of silencing is coordinated with thestructural changes in chromosomes that occur as cells progress through DNA replication and mitosis.  We are specifically investigating the influence of the cohesin and condensin proteins on silencing.

Sir2 function and metabolism
Sir2 is a histone-modifying enzyme essential for silencing in yeast.  We have discovered that GAPDH, a glycolysis enzyme, interacts with Sir2 and affects transcriptional silencing.  We are determining the mechanism of this regulation and exploring the general effects of metabolism on the efficiency of silencing in yeast.

Professor of Molecular Biology and Biochemistry

mhingorani@wesleyan.edu

http://mhingorani.faculty.wesleyan.edu/

My research group investigates the mechanisms of proteins that are responsible for DNA replication and repair. These proteins are essential for maintaining genomic and cellular integrity, and their malfunction is linked to diseases such as cancer. Currently our focus is on (a) S. cerevisiae and T. aquaticus DNA mismatch repair proteins that recognize errors/lesions in DNA and initiate repair or apoptosis, and (b) S. cerevisiae and E. coli clamp and clamp loader proteins that increase DNA replication efficiency help other proteins target sites of action on DNA. We utilize transient kinetic methods coupled with spectroscopy to examine the workings of these ATP-fueled protein machines. I teach courses in molecular biology, biochemistry, enzyme kinetics, and I am exploring cross-disciplinary education between the sciences and other academic disciplines through team-taught courses such as "Making the Science Documentary" with Jacob Bricca (Film Studies) and "Body Languages: Choreographing Biology" with Katja Kolcio (Dance).

Associate Professor of Molecular Biology and Biochemistry

rlane@wesleyan.edu

Research in the Lane lab is focussed on how large multi-gene families in mammalian genomes are utilized in the development of complex biological functions. Our specific focus is on the development of olfactory sensory perception, which depends on co-regulation of a very large olfactory receptor (OR) gene family (with >1000 gene members). The lab utilizes a variety of modern techniques in molecular genetics, cell biology, and comparative genomics to investigate the genetic and epigenetic mechanisms of OR transcriptional control.

http://rlane.faculty.wesleyan.edu/

Assistant Professor of Molecular Biology and Biochemistry

amacqueen@wesleyan.edu

http://macqueenlab.research.wesleyan.edu/

Our research seeks to understand the fundamental, yet long mysterious, cellular mechanisms that drive chromosome dynamics during the differentiation of sex cells (gametes).

Associate Professor of Molecular Biology and Biochemistry

mmcalear@wesleyan.edu

http://mmcalear.faculty.wesleyan.edu/

The McAlear lab's project is focused on understanding how cells respond to their environment by increasing or decreasing their capacity to produce proteins. Understanding the molecular mechanisms whereby cells turn on and off the machinery required for protein synthesis is vital for understanding how cells grow, divide, and divide abnormally including cancer. In particular, we have discovered that cells regulate gene expression, in part, by positioning a subset of the genes of individual regulons as immediate, adjacent gene pairs.

Professor of Molecular Biology and Biochemistry

Dean of Natural Sciences and Mathematics

imukerji@wesleyan.edu

http://imukerji.faculty.wesleyan.edu

Our research interests focus on the use of spectroscopic tools to investigate challenging problems in Biology by exploring the structure-function relationship of biomolecules. Current research areas include understanding the mechanisms of high affinity binding and recognition in protein-DNA interactions and the mechanisms of fiber and plaque formation in Alzheimer's disease.

http://www.sicklecellinfo.net

Visiting Assistant Professor of Molecular Biology and Biochemistry

mmurolo@wesleyan.edu

My research training in is the area of molecular microbiology.  My position at Wesleyan is teaching oriented.  I coordinate all of the Principles of Biology labs and teach in the fall Principles of Biology lecture program.

Daniel Ayres Professor of Biology

Professor of Molecular Biology and Biochemistry

doliver@wesleyan.edu

We are using the simple, well-characterized, and genetically facile bacterium E. coli as a model system to study the molecular details of protein translocation across the plasma membrane. Our major focus is on SecA ATPase, a DEAD motor protein that binds preproteins and the SecYEG channel complex, and which undergoes ATP-driven conformational cycles at the membrane that drive the stepwise translocation of proteins across the membrane. Genetic, biochemical and biophysical approaches are being utilized along with recent X-ray structures of SecA and SecYEG proteins in order to elucidate a number of important questions in this system: 1. SecA ATPase enzymology. SecA is a multi-domain protein whose conformational cycling is regulated by binding nucleotide, preproteins, SecYEG, and acidic phospholipids. SecA mutant proteins are being generated and utilized to define the enzymology of this complex ATPase. 2. SecA association with preproteins and SecYEG. Multidisciplinary approaches are being utilized to define the structural details of SecA interaction with signal peptides, preproteins, and SecYEG and to elucidate their functional consequences in order to work out the protein translocation cycle. 3. SecA dimer function. The nature of the requirement for SecA homo-dimerization in protein translocation is being elucidated.

Assistant Professor of Molecular Biology and Biochemistry

rolson@wesleyan.edu

My laboratory uses a combination of X-ray crystallography and complementary biophysical techniques to study the structure and function of integral and peripheral membrane proteins. I am particularly interested in two major questions- how do bacterial virulence factors facilitate host invasion by bacterial pathogens and how do neurological receptors identify and transduce chemical signals across the cell membrane? Driven by these questions, we are studying the structure and function of pore-forming toxins, bacterial virulence factors, and G-protein coupled-receptors. I currently teach courses on membrane protein structure and signal transduction.

http://rolson.faculty.wesleyan.edu/

http://www.wesleyan.edu/mbb/faculty/wfirshein/